Over the last several years it has become apparent that the neurotransmitter serotonin (5-hydroxytryptamine--5-HT) is associated directly or indirectly with a number of physiological phenomena, including appetite, memory, thermoregulation, sleep, sexual behavior, anxiety, depression, blood pressure lowering and hallucinogenic behavior [Glennon, R. A., J. Med. Chem., 30, 1 (1987)].
It has been recognized that there are multiple types of 5-HT receptors. These receptors have been classified as 5-HT.sub.1, 5-HT.sub.2, and 5-HT.sub.3 receptors, with the former being further divided into the subclasses 5-HT.sub.1A, 5-HT.sub.1B, 5-HT.sub.1C, and 5-HT.sub.1D. The binding affinity of a compound for one or more 5-HT receptors can provide a desirable physiological effect or minimize an undesirable effect. Therefore it is desirable to provide compounds which can bind to 5-HT receptors to act as serotonin agonists or antagonists.
Flaugh in U.S. Pat. No. 4,576,959 (issued 1986) disclosed a family of 6-substituted-4-dialkylamino-1,3,4,5-tetrahydrobenz[cd]indoles which are described as central serotonin agonists. Leander in U.S. Pat. No. 4,745,126 (1988) disclosed a method for treating anxiety in humans employing a 4-substituted-1,3,4,5-tetrahydrobenz[cd]indole-6-carboxamide derivative.
Certain indolines have been reported, as in U.S. Pat. No. 4,110,339 of Bach et al. (1978), Flaugh et al., J. Med. Chem., 31, pp 1746-1753 (1988), Flaugh in U.S. Pat. No. 4,576,959 and European Patent Application 153083 (published 1985). These were used as intermediates in the preparation of the corresponding indoles.
It has now been found that certain 6-substituted-and particularly 6-acyl-substituted-4-aminohexahydrobenz[cd]indoles (indolines) particularly certain stereoisomers of such indolines are useful in treating conditions requiring modification of serotonin function in the body.